P1071: IMPACT OF ACETYLSALICYLIC ACID DOSAGE ON INCIDENCE OF THROMBOSIS AND MORTALITY IN PATIENTS WITH MYELOPROLIFERATIVE NEOPLASMS.
Authors: A. Wild, S. Wimmerová
Journal: HemaSphere (2022)

Background: Bcr/abl – negative myeloproliferative neoplasms (MPN) are associated with a higher risk of thrombosis and higher vascular mortality. Acetylsalicylic acid (ASA) used in prevention decreases risk of vascular events in patients with MPN. There is some evidence that ASA in dose 100 mg once daily results in incomplete inhibition of a platelet function over the whole 24-hour interval in most patients with essential thrombocythemia (ET). High on-treatment reactivity (HOTR) was corrected with dosing ASA twice daily. Evidence of clinical consequences of these findings has been missing. Aims: Authors compared thrombosis incidence, mortality and safety among cohorts of MPN patients with adequate on-treatment reactivity (AOTR) on ASA dosed once daily, twice daily and patients with HOTR. Methods: Response to ASA in patients with MPN was evaluated by a platelet light transmission aggregometry induced by arachidonic acid. AOTR was defined as maximal amplitude up to 20% just before the next dose of ASA. In patients with HOTR, ASA dosing was changed to twice daily with a dose from 50 mg step by step up to 150 mg till AOTR was reached. A few patients didn´t change their doses at their own decision despite HOTR. The patients were regularly followed-up. Incidence of thrombosis, adverse events and mortality were compared among the cohorts. Results: The platelet aggregation was tested in 69 patients with MPN on ASA. Patients with ET, polycythemia vera (PV), primary myelofibrosis, post-PV plus post-ET myelofibrosis and MPN not otherwise specified presented 16, 42, 36, 5 and 1%, respectively. The adequate responses (AOTR) were found in 57 (83%), cohort 1. The insufficient responses were found in 12 persons (17%), in 30% of patients on an enterosolvent form of ASA. In these 12 patients the dose of ASA was changed to 2x50mg in 4 and to 2x100mg in 1 patient (cohort 2) and remained unchanged in seven (cohort 3). There were no differences in frequency of risk factors besides higher frequency of diabetes mellitus in group 3 compared to group 1 (p=0,021). Non-adherence to regular administration of ASA was found in 10% of patients. The follow-up was 36,8 months. All-cause mortality was higher in the cohort 3 compared to the cohort 1 (p=0,009), see fig. 1, but thrombotic episodes incidence not. The cohort 2 had not different incidence of both thrombotic episodes and deaths compared to the cohort 1. No proximal gastrointestinal bleeding and other gastropathies occurred. There was no bleeding episode on ASA in dose of 2x50mg daily. A non-severe bleeding dependant on any ASA dose were found. Repeated measurement of platelet aggregation was done in 29 patients in median 49,5 months after previous measurements. There was no statistically significant difference of adequate/high platelet reactivity on ASA between the first and the last measurement. Image:Summary/Conclusion: The frequency of MPN patients with higher platelet reactivity on ASA was lower than in the most data in literature. Correction of an ASA dosage to twice daily reaching AOTR resulted in lower mortality. Other studies are required to confirm these data. Initial dose 2x50mg seems to be effective and safer than higher dosage. The long-term reproducibility of platelet aggregation testing results was preserved.